This project has been completed. It originated from a previous observation of a simultaneous induction of the metastatic phenotype and increased type IV collagenolytic activity in ras transfected NIH/3T3 cells. Here a N-nitrosomethylurea induced rat mammary carcinoma model was used to study the relationship between ras levels, metalloproteinase expression and metastatic behavior. When comparing normal and malignant rat breast tissues, there was no direct relationship between ras DNA levels and neoplastic development, or between metastatic and nonmetastatic rat mammary carcinomas. Two major gelatinolytic metalloproteinases (gelatinases) of 65 and 92kDa were present in the carcinomas, but only the 65kDa gelatinase was detected in normal breast tissues and a rat fibroma. Type IV collagenolytic activity in tissue lysates from the carcinomas was two to three times higher than that of normal breasts, but primary tumors did not differ from their corresponding metastases. In this carcinogenically induced metastatic rat mammary carcinoma model, we have demonstrated that ras amplification is not necessary for the development of the malignant or metastatic phenotype. Furthermore, we have discovered through a glucocorticoid promoter mediated induction of the p2l ras protein that increased ras expression does not lead to an increase in metastatic capacity.